Genital lichen planus: Adding to the review of an "underrecognized entity".

Sir,

The dilemma posed by nonvenereal genital dermatoses supersedes the number of differential diagnosis of genital erosive lesions. The importance of being exhaustive and factually correct, while reviewing an uncommon condition such as genital lichen planus (GLP) needs no overemphasis. We wish to add on to the inadequacies and rectify the errors that regrettably reduced the utility of an otherwise nicely authored review by Khurana et al.[1]

Authors referred to the retrospective study of 100 women diagnosed at Mayo clinic with vulval LP (VLP) by Fahy et al.[2] (reference no. 11) erroneously as “A more recent publication, however, found histologically confirmed VLP in 57% of 42 female patients with oral LP (OLP). About 62% of those found to have lesions of VLP were symptomatic, while in 38%, the disease was asymptomatic.”[1] Erroneous referencing caused confusion while reading. We would also like to comment on the assertion made by the authors that VLP “has not been reported before puberty.”[1] In their series of 316 Indian childhood patients of LP, Pandhi et al. have reported VLP in four young girls.[3]

We expected that the review article would highlight epidemiological statistics regarding the relative incidence of oral, genital, and cutaneous LP with an analytical approach. For example, authors quoted disparage figures of the incidence rates of the presence of GLP in patients with OLP from select studies without any criteria or specialty characteristic of those studies. We were sincerely hoping that a categorical distinction would be mentioned of whether the detection of GLP in these studies was based on purely clinical suspicion or histological confirmation. The diagnostic criteria-based rates rather than the chronology of the published results would have revealed a more realistic association among these three types of LP. Given the scarcity of literature specific to GLP, the discussion on the etiology of GLP referred to that of OLP.[1] As a corollary, for a data-poor condition like GLP, any factor(s) stated/suggested in any previous publication to be of GLP-specific etiological significance irrespective of statistical significance (such as psychological comorbiditiy) merits mention in a review addressing the rare disease. The speculation that patients with both genital and oral involvement and severely symptomatic disease may represent a distinct genetic cohort with higher association of psychosocial morbidity (i.e., higher frequency and severity of anxiety and depression) has been backed with strong evidence.[4] High rate of poor psychoevaluation scores has been reported in patients with not only concomitant OLP and GLP but also isolated GLP, which warrants serious consideration of this aspect to deliver holistic therapy to such patients. Authors should have also dwelled upon the strongly suspected association between erosive GLP and herpetic infection. Although this association needs further exploration, high titers of antiherpetic antibodies reported in more than 60% of mucosal LP patients (oral ± genital) with severe burning symptoms deserved mention.[4]

We would also like to humbly share certain additional points worth consideration (both from published literature, and our own experience) in the diagnostic approach, and therapeutic modalities for this condition. We strongly recommend the use of dermoscopic evaluation (or in this context, the diagnostic approach might better be referred to as genital mucoscopy), as a pre-biopsy non-invasive diagnostic aid. Although a tissue diagnosis must always be done through mucosal biopsy if the clinicodermoscopic diagnosis is doubtful, initial mucoscopic evaluation using a hand-held or USB-videodermatoscope in non-polarized, as well as non-contact polarized mode can be a very useful tool for planning the overall approach to management. While it may obviate the need for biopsy (when assessed by an experienced dermoscopist), in other cases, it may serve as a tool to decide the site of biopsy likely to be most yieldful, and also help in convincing an anxious patient regarding the necessity of biopsy. Despite histopathology remaining the gold standard of cutaneous diagnosis, the avoidance of the serious psychological impact of a genital biopsy and published dermoscopic patterns capable of decent differentiation of GLP from close differentials[5] make dermoscopy as the first-line diagnostic approach for GLP. Figure 1 demonstrates the classical dermoscopic features seen in vulvar LP, lichen sclerosus et atrophicus (LSA), and plasma cell mucositis, respectively. We advise the esteemed journal readers to refer to the article on dermoscopic differentiation of inflammatory genital dermatoses including GLP by Borghi et al.[5]

Figure 1

Noninvasive differentiation of genital lichen planus on dermoscopy. Classic dermoscopic features of three common vulvar dermatoses: (a) vulvar lichen planus demonstrating an intense red background with multiple foci of homogenous to reticuloglobular Wickham's striae or WS (black arrow), diffusely arranged thick linear, curvilinear, and branching vessels, and diffuse faint bluish-gray peppering that have evolved into focal bluish-gray-to-brown colored pigmented structureless areas (white arrow); (b) vulvar lichen sclerosus showing a pinkish-white background with multiple patchy whitish structureless areas, and although few linear and curved vessels are visible overall, the concentration of vessels is markedly reduced; and (c) vulvar plasma cell mucositis displaying diffuse and focal reddish-orange structureless areas with prominent convoluted and serpentine vessels (Escope Videodermatoscope, ×55, polarised; Timpac Healthcare, New Delhi)

In topicals, azoles may better be replaced with a stable formulation cream of ciclopirox olamine (CPO) 1%, for various reasons. Not only CPO has been reported to exert potent fungicidal effect compared to fungistatic effect of azoles over yeasts, the spectrum of antifungal coverage by CPO is much broader than azoles; with studies confirming CPO as a much more potent antimycotic against with lowest minimum inhibitory concentration (MIC) values against 14 different strains of Candida (including azole-resistant Candida albicans and other species).[6] It is important to mention few more important collateral advantages of preferring CPO in management of genital LP in both genders but more so in women, both during initial aggressive control with potent topical corticosteroid (TCS) like clobetasol, as well as sole or adjuvant topical agent for providing steroid-free maintenance of remission of lesions. The CPO cream additionally exerts potent poly-antimicrobial effects, providing clinically significant protection against multiple gram positive and gram negative bacteria (implicated in aerobic vaginitis), Gardnerella vaginalis (main species implicated in bacterial vaginosis), and Trichomonas vaginalis (responsible for trichomoniasis) while sparing Lactobacilli spp. thereby maintaining a healthy vaginal microbiome (VMB) despite TCS-associated compromised local immunity of eroded lesions. The potent inhibitory effects of CPO on the multiplication of three viral agents (Herpes simplex viruses, human papilloma virus, and human immunodeficiency virus or HIV-1) that are known to often secondarily invade any eroded mucosal lesion (like genital LP) being treated with potent topical and/or oral steroids or non-steroidal immunosuppressive agents suggests CPO 1% cream as the front-runner topical adjuvant to TCS/topical CNI initially, and as maintenance topical in the long term. Furthermore, the potent anti-inflammatory activity of 1% CPO (mediated via inhibition of prostaglandin and leukotriene synthesis in human polymorphonuclear cells - reported to be higher than most of the other topical antimycotics including azoles, polyenes, and allylamines, and found comparable to indomethacin, desoximetasone, and even 2.5% hydrocortisone), and expedited wound healing properties (mediated via stabilization/alteration in cellular oxygen-sensitive factors, and enhanced angiogenesis)[6] reinforce that the veritable potential of 1% CPO as maintenance therapy for genital LP. In authors’ collective experience, after inducing remission in erosive/ulcerated genital LP lesions with topical and/or systemic CS or steroid sparing immunomodulator agents, long term maintenance (upto 6 months) has been successfully maintained only with once-a-day CPO 1% cream application in addition to local hygiene (unpublished data). Anecdotal, and some conflicting evidence exists about modest to good response of genital mucosal LP (whether present in isolation or more commonly with diffuse cutaneous LP) to aloe vera gel, oral tacrolimus, oral metronidazole, oral sulfasalazine, subcutaneous low molecular-weight heparin (enoxaparin 3-5 mg/week), adalimumab, rituximab, focused ultrasound therapy, and the latest being oral apremilast.[7] Although the latter has the advantage of insignificant adverse effects, and no need for regular laboratory monitoring, the evidence in its favour as a therapy for genital LP is scant as of now.

In conclusion, we attempted to supplant the facts and information necessary in a review of genital LP. We would also suggest that the authors consider corrections and an erratum for the assertions/references stated in the review for the benefit of readers. We humbly request all authors of a review article, especially dealing with an “underrecognized entity” like genital LP, to be meticulous in their search, analysis, and interpretation of literature. Only such approach can serve the true purpose of educating the readers with resultant improved patient detection and management.

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Nil.

Conflicts of interest

There are no conflicts of interest.